Process for preparation of 5-bromo-1,3-dichloro-2-fluoro-benzene

ABSTRACT

The invention relates to a process for the preparation of 5-bromo-1,3-dichloro-2-fluoro-benzene by diazotization and reduction of 6-bromo-2,4-dichloro-3-fluoro-aniline, which is obtained by bromination of 2,4-dichloro-3-fluoro-aniline, which is obtained by reduction of 1,3-dichloro-2-fluoro-4-nitro-benzene, and a process for preparing active compounds of formula V (Formula V) wherein the variables are defined in the specification by further transforming 5-bromo-1,3-dichloro-2-fluoro-benzene obtained from 2,4-dichloro-3-fluoro-aniline by the process according to the invention.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is the U.S. national phase of International Application No. PCT/EP2019/082352, filed Nov. 25, 2019, which claims the benefit of European Patent Application No. 18209956.4, filed on Dec. 4, 2018.

The invention relates to a process for the preparation of 5-bromo-1,3-dichloro-2-fluoro-benzene of formula I

by diazotization and reduction of 6-bromo-2,4-dichloro-3-fluoro-aniline of formula II,

6-bromo-2,4-dichloro-3-fluoro-aniline of formula II is obtained by bromination of 2,4-dichloro-3-fluoro-aniline of formula III.

2,4-dichloro-3-fluoro-aniline of formula III is obtained by reduction of 1,3-dichloro-2-fluoro-4-nitro-benzene of formula IV.

Compound of formula I is a valuable intermediate for the preparation of active compounds of formula V

-   wherein -   X is CH, O, or S, -   U is CH or N;

G¹, G² are each CR³, or together form a sulfur atom; ze

-   each R³ is independently H, halogen, CN, N₃, NO₂, SCN, SF₅,     C₁-C₆-alkyl, C₃-C₈-cycloalkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, which     groups are unsubstituted, partially or fully halogenated and/or     substituted with one or more same or different R⁸,     -   Si(R¹²)₃, OR⁹, S(O)_(n)R⁹, NR^(10a)R^(10b),     -   phenyl which is unsubstituted or partially or fully substituted         with R¹¹, and a 3- to 10-membered saturated, partially or fully         unsaturated heteromonocyclic or heterobicyclic ring containing         1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, which         ring is unsubstituted, or substituted with one or more same or         different R¹¹, preferably the unsubstituted or substituted HET; -   n is 0, 1, or 2; -   or two R³ bonded to adjacent carbon atoms may form a five- or six     membered saturated, partially or fully unsaturated carbocyclic ring,     or a dihydrofuran, or     -   R³ bonded to carbon atom in position G¹ form a bond to the chain         *-Q-Z— in group A²; -   A is a group A¹, A², A³, or A⁴; wherein     -   A¹ is C(═W)Y;         -   W is O, or S;         -   Y is N(R⁵)R⁶, or OR⁹;     -   A² is

-   -   -   wherein #denotes the bond of group A, and % denotes the bond             to G¹;         -   Q-Z is %—CH₂—O—*, %—CH₂—S(O)_(n)—*, or %—C(═O)—O—*, wherein             % marks the bond of Q to phenyl, and *the bond of Z to             azetidin; and         -   R^(A4) is H or C(═O)R^(4A), wherein             -   R^(4A) is H, C₁-C₆-alkyl, C₁-C₆-haloalkyl,                 C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl,                 C₂-C₆-haloalkynyl, C₁-C₄-alkylcarbonyl, which aliphatic                 groups are unsubstituted or substituted with one or more                 radicals R⁴¹; C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl                 which cyclic groups are unsubstituted or substituted                 with one or more R⁴²;                 -   C(═O)N(R⁴³)R⁴⁴, N(R⁴³)R⁴⁵, CH═NOR⁴⁶;                 -   phenyl, heterocycle, or hetaryl HET which rings are                     unsubstituted or partially or fully substituted with                     R^(A);             -   R⁴¹ is independently OH, CN, C₁-C₆-alkoxy,                 C₁-C₆-haloalkoxy, S(O)_(n)—C₁-C₆-alkyl,                 S(O)_(n)—C₁-C₆-haloalkyl, C(═O)N(R⁴³)R⁴⁴,                 -   C₃-C₆-cycloalkyl, or C₃-C₆-halocycloalkyl which                     cycles are unsubstituted or substituted with one or                     more R⁴¹¹; or                 -   phenyl, heterocycle or hetaryl HET which rings are                     unsubstituted or partially or fully substituted with                     R^(A);             -   R⁴¹¹ is independently OH, CN, C₁-C₂-alkyl, or                 C₁-C₂-haloalkyl;             -   R⁴³ is H, or C₁-C₆-alkyl,             -   R⁴⁴ is H, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₆-alkenyl,                 C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, C₂-C₆-haloalkynyl, or                 C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl,                 C₃-C₆-cycloalkylmethyl, or C₃-C₆-halocycloalkylmethyl                 which rings are unsubstituted or substituted with a                 cyano;             -   R⁴⁵ H, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₄-alkenyl,                 C₂-C₄-alkynyl, CH₂—CN, C₃-C₆-cycloalkyl,                 C₃-C₆-halocycloalkyl, C₃-C₆-cycloalkylmethyl,                 C₃-C₆-halocycloalkylmethyl, phenyl and hetaryl HET which                 aromatic rings are unsubstituted or partially or fully                 substituted with R^(A);             -   R⁴² C₁-C₆-alkyl, C₁-C₆-haloalkyl, or a group as defined                 for R⁴¹;             -   R⁴⁶ is independently H, C₁-C₆-alkyl, or C₁-C₆-haloalkyl;             -   R^(A) is independently selected from halogen, CN, NO₂,                 C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₂-C₄-alkenyl,                 C₂-C₄-haloalkenyl, C₂-C₄-alkynyl, C₂-C₄-haloalkynyl,                 C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, C₁-C₄-alkoxy,                 C₁-C₄-haloalkoxy, S(O)_(n)—C₁-C₄-alkyl,                 S(O)_(n)—C₁-C₄-haloalkyl, C₁-C₄-alkylcarbonyl,                 C₁-C₄-haloalkylcarbonyl, C(═O)N(R⁴³)R⁴⁴; or             -   two R^(A) present on the same carbon atom of a saturated                 or partially saturated ring may form together ═O or ═S;                 or             -   two R^(A) present on the same S or SO ring member of a                 heterocyclic ring may together form a group                 ═N(C₁-C₆-alkyl), ═NO(C₁-C₆-alkyl), ═NN(H)(C₁-C₆-alkyl)                 or ═NN(C₁-C₆-alkyl)₂;

    -   A³ is CH₂—NR⁵C(═W)R⁶;

    -   A⁴ is cyano;

    -   R⁵ is independently selected from the meanings mentioned for R²;

    -   R⁶ is H, CN, C₁-C₁₀-alkyl, C₃-C₈-cycloalkyl, C₂-C₁₀-alkenyl,         C₂-C₁₀-alkynyl, which groups are unsubstituted, partially or         fully halogenated and/or substituted with one or more same or         different R⁸;         -   or S(O)_(n)R⁹, or C(═O)R⁸;         -   a 3- to 8-membered saturated, partially or fully unsaturated             heterocyclic ring, which ring may contain 1, 2, 3, or 4             heteroatoms O, S, N, C═O and/or C═S as ring members, which             heterocyclic ring is unsubstituted or partially or fully             substituted with same or different halogen, CN, C₁-C₆-alkyl,             C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy,             C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, C₃-C₈-cycloalkyl,             C₃-C₈-halocycloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl,             C₂-C₆-alkynyl, C₂-C₆-haloalkynyl, which groups are             unsubstituted, or partially or fully substituted with same             or different R⁸, or phenyl which may be partially or fully             substituted with R¹¹;

    -   or R⁵ and R⁶, together with the nitrogen atom to which they are         bound, form a 3- to 8-membered saturated, partially or fully         unsaturated heterocyclic ring, which ring may contain 1, 2, 3,         or 4 heteroatoms O, S, N, C═O and/or C═S as ring members, which         heterocyclic ring is unsubstituted or partially or fully         substituted with same or different halogen, CN, C₁-C₆-alkyl,         C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy,         C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, C₃-C₈-cycloalkyl,         C₃-C₈-halocycloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl,         C₂-C₆-alkynyl, C₂-C₆-haloalkynyl, which groups are         unsubstituted, or partially or fully substituted with same or         different R⁸, or phenyl which may be partially or fully         substituted with R¹¹;

    -   or R⁵ and R⁶ together form a group ═C(R⁸)₂, ═S(O)_(m)(R⁹)₂,         ═NR^(10a), or ═NOR⁹;

    -   R^(7a), R^(7b) are each independently H, halogen, CN,         C₁-C₆-alkyl, C₃-C₈-cycloalkyl, C₂-C₆-alkenyl, or C₂-C₆-alkynyl,         which groups are unsubstituted, partially or fully halogenated         and/or substituted with same or different R⁸;

    -   each R⁸ is independently CN, N₃, NO₂, SCN, SF₅,         C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl, wherein the carbon         chains may be substituted with one or more R¹³;         -   Si(R¹²)₃, OR⁹, OSO₂R⁹, S(O)_(n)R⁹, N(R^(10a))R^(10b),             C(═O)N(R^(10a))R^(10b),         -   C(═S)N(R^(10a))R^(10b), C(═O)OR⁹, CH═NOR⁹,         -   phenyl, which is unsubstituted or partially or fully             substituted with same or different R¹⁶, or         -   a 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully             unsaturated heterocyclic ring comprising 1, 2 or 3             heteroatoms N, O, and/or S as ring members, which ring is             unsubstituted or partially or fully substituted with same or             different R¹⁶, or

    -   two R⁸ present on the same carbon atom of an alkyl, alkenyl,         alkynyl or cycloalkyl group together form a group ═O, ═C(R¹³)₂;         ═S; ═S(O)_(m)(R¹⁵)₂, ═S(O)_(m)R¹⁵N(R^(14a))R^(14b), ═NR^(10a),         ═NOR⁹; or ═NN(R^(10a))R^(10b); or

    -   two radicals R⁸, together with the carbon atoms of the alkyl,         alkenyl, alkynyl or cycloalkyl group which they are bonded to,         form a 3-, 4-, 5-, 6-, 7- or 8-membered saturated or partially         unsaturated carbocyclic or heterocyclic ring, which heterocyclic         ring comprises 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring         members, and which ring is unsubstituted, or partially or fully         substituted with same or different R¹⁶; and

    -   R⁸ as a substituent on a cycloalkyl ring may additionally be         C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl,         C₂-C₆-alkynyl, and C₂-C₆-haloalkynyl, which groups are         unsubstituted, or partially or fully substituted with same or         different R¹³; and

    -   R⁸ in the groups C(═O)R⁸ and ═C(R⁸)₂ may additionally be H,         halogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₆-alkenyl,         C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, or C₂-C₆-haloalkynyl, which         groups are unsubstituted, or partially or fully substituted with         same or different R¹³;

    -   each R⁹ is independently H, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl,         C₃-C₈-cycloalkyl, C₃-C₈-cycloalkyl-C₁-C₄-alkyl-,         C₃-C₈-halocycloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl,         C₂-C₆-alkynyl, or C₂-C₆-haloalkynyl, which groups are         unsubstituted, or partially or fully substituted with same or         different R¹³, or         -   C₁-C₆-alkyl-C(═O)OR¹⁵, C₁-C₆-alkyl-C(═O)N(R^(14a))R^(14b),             C₁-C₆-alkyl-C(═S)N(R^(14a))R^(14b),         -   C₁-C₆-alkyl-C(═NR¹⁴)N(R^(14a))R^(14b), Si(R¹²)₃,             S(O)_(n)R¹⁵, S(O)_(n)N(R^(14a))R^(14b), N(R^(10a))R^(10b),             N═C(R¹³)₂, C(═O)R¹³, C(═O)N(R^(14a))R^(14b),             C(═S)N(R^(14a))R^(14b), C(═O)OR¹⁵, or         -   phenyl, which is unsubstituted, or partially or fully             substituted with R¹⁶; and         -   a 3- to 7-membered saturated, partially or fully unsaturated             heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O,             and/or S as ring members, which ring is unsubstituted, or             partially or fully substituted with same or different R¹⁶;             and

    -   R⁹ in the groups S(O)_(n)R⁹ and OSO₂R⁹ may additionally be         C₁-C₆-alkoxy, or C₁-C₆-haloalkoxy;

    -   R^(10a), R^(10b) are independently from one another H,         C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₃-C₈-cycloalkyl,         C₃-C₈-halocycloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl,         C₂-C₆-alkynyl, C₂-C₆-haloalkynyl, which groups are         unsubstituted, or partially or fully substituted with same or         different R¹³;         -   C₁-C₆-alkyl-C(═O)OR¹⁵, C₁-C₆-alkyl-C(═O)N(R^(14a))R^(14b),             C₁-C₆-alkyl-C(═S)N(R^(14a))R^(14b),         -   C₁-C₆-alkyl-C(═NR¹⁴)N(R^(14a))R^(14b), C₁-C₆-alkoxy,             C₁-C₆-haloalkoxy, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio,             S(O)_(n)R¹⁵, S(O)_(n)N(R^(14a))R^(14b), C(═O)R¹³, C(═O)OR¹⁵,         -   C(═O)N(R^(14a))R^(14b),         -   C(═S)R¹³, C(═S)SR¹⁵, C(═S)N(R^(14a))R^(14b), C(═NR¹⁴)R¹³;         -   phenyl, which is unsubstituted, or partially or fully             substituted with same or different R¹⁶; and         -   a 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully             unsaturated heterocyclic ring comprising 1, 2, 3 or 4             heteroatoms N, O, and/or S as ring members, which ring is             unsubstituted, or partially or fully substituted with same             or different R¹⁶, preferably unsubstituted or substituted             HET; or

    -   R^(10a) and R^(10b) together with the nitrogen atom they are         bonded to form a 3- to 8-membered saturated, partially or fully         unsaturated heterocyclic ring, which ring may additionally         contain one or two heteroatoms N, O, and/or S as ring members,         which ring is unsubstituted, or partially or fully substituted         with same or different halogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl,         C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkylthio,         C₁-C₆-haloalkylthio, C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl,         C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl,         C₂-C₆-haloalkynyl, phenyl which may be partially or fully         substituted with R¹⁶, and a 3-, 4-, 5-, 6-, or 7-membered         saturated, partially or fully unsaturated heterocyclic ring         comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members,         which ring is unsubstituted, or partially or fully substituted         with same or different R¹⁶; or

    -   R^(10a) and R^(10b) together form a group ═C(R¹³)₂,         ═S(O)_(m)(R¹⁵)₂, ═S(O)_(m)R¹⁵N(R^(14a))R^(14b), ═NR, or ═NOR¹⁵;

    -   R¹¹ is halogen, CN, N₃, NO₂, SCN, SF₅, C₁-C₁₀-alkyl,         C₃-C₈-cycloalkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, which groups         are unsubstituted, partially or fully halogenated, and/or may be         substituted with same or different R⁸, or         -   OR⁹, NR^(10a)R^(10b), S(O)_(n)R⁹, Si(R¹²)₃;         -   phenyl, which is unsubstituted, or partially or fully             substituted with same or different R¹⁶; and         -   a 3- to 7-membered saturated, partially or fully unsaturated             aromatic heterocyclic ring comprising 1, 2, 3, or 4             heteroatoms N, O, and/or S as ring members, which ring is             unsubstituted, or partially or fully substituted with same             or different R¹⁶; or

    -   two R¹¹ present on the same ring carbon atom of an unsaturated         or partially unsaturated heterocyclic ring may together form a         group ═O, ═C(R¹³)₂, ═S, ═S(O)_(m)(R¹⁵)₂,         ═S(O)_(m)R¹⁵N(R^(14a))R^(14b), ═NR¹⁴, ═NOR¹⁵, or         ═NN(R^(14a))R^(14b);

    -   or two R¹¹ bound on adjacent ring atoms form together with the         ring atoms to which they are bound a saturated 3- to 9-membered         ring, which ring may contain 1 or 2 heteroatoms O, S, N, and/or         NR¹⁴, and/or 1 or 2 groups C═O, C═S, C═NR¹⁴ as ring members, and         which ring is unsubstituted, or partially or fully substituted         with same or different halogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl,         C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkylthio,         C₁-C₆-haloalkylthio, C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl,         C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl,         C₂-C₆-haloalkynyl, phenyl which may be partially or fully         substituted with same or different R¹⁶, and a 3- to 7-membered         saturated, partially or fully unsaturated heterocyclic ring         containing 1, 2, or 3 heteroatoms N, O, and/or S as ring         members, which ring is unsubstituted, or partially or fully         substituted with same or different R¹⁶;

    -   each R¹² is independently C₁-C₄-alkyl and phenyl, which is         unsubstituted, or partially or fully substituted with same or         different C₁-C₄-alkyl;

    -   each R¹³ is independently CN, NO₂, OH, SH, SCN, SF₅,         C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, SO_(n)—C₁-C₆-alkyl,         SO_(n)—C₁-C₆-haloalkyl, Si(R¹²)₃, —C(═O)N(R^(14a))R^(14b),         -   C₃-C₈-cycloalkyl which is unsubstituted, partially or fully             halogenated or substituted with 1 or 2 same or different             C₁-C₄-alkyl, C₃-C₄-cycloalkyl, C₁-C₄-alkoxy,             C₁-C₄-haloalkoxy and/or oxo; phenyl, benzyl, phenoxy, where             the phenyl moiety may be substituted with one or more same             or different R¹⁶; and a 3- to 7-membered saturated,             partially or fully unsaturated heterocyclic ring containing             1, 2, or 3 heteroatoms N, O, and/or S, as ring members,             which ring is unsubstituted, or partially or fully             substituted with same or different R¹⁶; or

    -   two R¹³ present on the same carbon atom of an alkyl, alkenyl,         alkynyl or cycloalkyl group may together be ═O,         ═CH(C₁-C₄-alkyl), ═C(C₁-C₄-alkyl)C₁-C₄-alkyl, ═N(C₁-C₆-alkyl) or         ═NO(C₁-C₆-alkyl); and

    -   R¹³ as a substituent of a cycloalkyl ring may additionally be         C₁-C₆-alkyl, C₂-C₆-alkenyl or C₂-C₆-alkynyl, which groups are         unsubstituted, partially or fully halogenated, or substituted         with 1 or 2 CN, C₃-C₄-cycloalkyl, C₁-C₄-alkoxy,         C₁-C₄-haloalkoxy, and oxo; and

    -   R¹³ in groups ═C(R¹³)₂, N═C(R¹³)₂, C(═O)R¹³, C(═S)R¹³, and         C(═NR¹⁴)R¹³ may additionally be H, halogen, C₁-C₆-alkyl,         C₂-C₆-alkenyl, or C₂-C₆-alkynyl, which groups are unsubstituted,         partially or fully halogenated, or substituted with 1 or 2 CN,         C₃-C₄-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, and oxo;

    -   each R¹⁴ is independently H, CN, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy,         SO_(n)—C₁-C₆-alkyl, SO_(n)—C₁-C₆-haloalkyl, Si(R¹²)₃;         -   C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, which groups are             unsubstituted, partially or fully halogenated, or             substituted with 1 or 2 CN, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy,             SO_(n)—C₁-C₄-alkyl, C₃-C₆-cycloalkyl which is unsubstituted             or substituted with 1 or 2 substituents halogen and CN;         -   and oxo;         -   C₃-C₈-cycloalkyl which is unsubstituted, or partially or             fully halogenated or substituted with 1 or 2 CN,             C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy,             SO_(n)—C₁-C₆-alkyl, C₃-C₄-cycloalkyl,             C₃-C₄-cycloalkyl-C₁-C₄-alkyl-, which groups are             unsubstituted, or substituted with 1 or 2 substituents             selected from halogen and CN;         -   phenyl, benzyl, pyridyl, phenoxy, which cyclic moieties are             unsubstituted, or substituted with one or more same or             different halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl,             C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkylthio,             C₁-C₆-haloalkylthio, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl,             C₂-C₄-alkynyl, C₂-C₄-haloalkynyl, C₃-C₆-cycloalkyl,             C₃-C₆-halocycloalkyl, and C₁-C₆-alkoxycarbonyl; and a 3-,             4-, 5- or 6-membered saturated, partially or fully             unsaturated heterocyclic ring comprising 1, 2 or 3             heteroatoms N, O, and/or S as ring members, which ring is             unsubstituted, or partially or fully substituted with same             or different R¹⁶;

    -   R^(14a) and R^(14b) independently of each other, have one of the         meanings given for R¹⁴; or

    -   R^(14a) and R^(14b), together with the nitrogen atom to which         they are bound, form a 3- to 7-membered saturated, partially, or         fully unsaturated heterocyclic ring, wherein the ring may         additionally contain 1 or 2 heteroatoms N, O, and/or S as ring         members, which ring is unsubstituted, or partially or fully         substituted with same or different halogen, C₁-C₄-alkyl,         C₁-C₄-haloalkyl, C₁-C₄-alkoxy, or C₁-C₄-haloalkoxy; or

    -   R^(14a) and R¹⁴ or R^(14b) and R¹⁴, together with the nitrogen         atoms to which they are bound in the group         C(═NR¹⁴)N(R^(14a))R^(14b), form a 3- to 7-membered partially, or         fully unsaturated heterocyclic ring, wherein the ring may         additionally contain 1 or 2 heteroatoms N, O, and/or S as ring         members, which ring is unsubstituted, or partially or fully         substituted with same or different halogen, C₁-C₄-haloalkyl,         C₁-C₄-alkoxy, or C₁-C₄-haloalkoxy;

    -   each R¹⁵ is independently H, CN, Si(R¹²)₃         -   C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, which groups are             unsubstituted, partially or fully halogenated, or             substituted with 1 or 2 radicals C₃-C₄-cycloalkyl,             C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, SO_(n)—C₁-C₆-alkyl, or oxo;         -   C₃-C₈-cycloalkyl which is unsubstituted, partially or fully             halogenated or substituted with 1 or 2 radicals C₁-C₄-alkyl,             C₃-C₄-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy,             SO_(n)—C₁-C₆-alkyl, or oxo;         -   phenyl, benzyl, pyridyl, and phenoxy, which rings are             unsubstituted, partially or fully halogenated, or             substituted with 1, 2 or 3 substituents C₁-C₆-alkyl,             C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, or             (C₁-C₆-alkoxy)carbonyl;

    -   each R¹⁶ is independently halogen, NO₂, CN, OH, SH,         C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, SO_(n)—C₁-C₆-alkyl,         SO_(n)—C₁-C₆-haloalkyl, C₁-C₄-alkylcarbonyl,         C₁-C₄-haloalkylcarbonyl, C₁-C₄-alkoxycarbonyl,         C₁-C₄-haloalkoxycarbonyl, aminocarbonyl,         C₁-C₄-alkylaminocarbonyl, di-(C₁-C₄-alkyl)-aminocarbonyl,         Si(R¹²)₃;         -   C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, which groups are             unsubstituted, partially or fully halogenated, or             substituted with 1 or 2 radicals CN, C₃-C₄-cycloalkyl,             C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, or oxo;         -   C₃-C₈-cycloalkyl which is unsubstituted, partially or fully             halogenated or substituted with 1 or 2 radicals CN,             C₁-C₄-alkyl, C₃-C₄-cycloalkyl, C₁-C₄-alkoxy,             C₁-C₄-haloalkoxy, or oxo;         -   phenyl, benzyl, pyridyl and phenoxy, which rings are             unsubstituted, partially or fully halogenated, or             substituted with 1, 2 or 3 substituents C₁-C₆-alkyl,             C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, or             (C₁-C₆-alkoxy)carbonyl; or

    -   two R¹⁶ present together on the same atom of an unsaturated or         partially unsaturated ring may be ═O, ═S, ═N(C₁-C₆-alkyl),         ═NO—C₁-C₆-alkyl, ═CH(C₁-C₄-alkyl), or ═C(C₁-C₄-alkyl)₂; or

    -   two R¹⁶ on two adjacent carbon atoms form together with the         carbon atoms they are bonded to a 4- to 8-membered saturated,         partially or fully unsaturated ring, wherein the ring may         contain 1 or 2 heteroatoms N, O, and/or S as ring members, which         ring is unsubstituted, or partially or fully substituted with         same or different halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,         C₁-C₄-alkoxy, or C₁-C₄-haloalkoxy;

    -   each m is independently 0, or 1.

Compounds V are known from WO 2013/026929, WO 2012/163959, WO 2012/007426, WO 2011/067272, WO 2010/149506, WO 2010/020522, WO 2009/080250, WO 2016/102482, and EP-A-1731512 to have pesticidal activity.

CN 103664511 discloses a method for preparation of compound I by fluorine Sandmeyer reaction starting from 3,5-dichloro-4-fluoro-aniline VI. However, compound VI of the above process is formed by a nitration reaction of dichlorofluorobenzene in an unselective nitration reaction, which is low yielding and gives a mixture of nitro isomers. After separation and isolation of the desired isomer and reduction of the nitro group, aniline compound VI can be obtained.

WO 2016/058895 discloses deprotonation of 1-bromo-4-fluoro-benzene with a magnesium amide base and reaction with a halogenating agent to yield compound I. However, the employed base involves lithium salts which are expensive on large scale. The described catalysts include hexamethyl phosphoric acid triamide, which is highly carcinogenic. The selectivity of the chlorination as described in the provided protocol is up to 12:1 and requires purification measures by silica gel chromatography. Such purification is difficult to be performed on large scale. Hence this process is not applicable to manufacture in industrial scale.

The objective task of the invention is providing an economical, industrially applicable manufacturing process for synthesis of 5-bromo-1,3-dichloro-2-fluoro-benzene. Accordingly, the above defined process was found.

In the inventive process 5-bromo-1,3-dichloro-2-fluoro-benzene 6-bromo-2,4-dichloro-3-fluoro-aniline is diazotized under acidic conditions to the salt of formula IIa wherein X⁻ is a counteranion of the acid, preferably a chloride anion, which salt is then reduced to 5-bromo-1,3-dichloro-2-fluoro-benzene

The diazotization is usually carried out at temperatures of from −20° C. to +20° C., preferably from −10° C. to +10° C., in an inert solvent, in the presence of alkali metal and alkaline earth metal nitrites or organic nitrites, such as methyl nitrite, ethyl nitrite, n-propyl nitrite, isopropyl nitrite, n-butylnitrite, sec-butyl nitrite, isobutyl nitrite, tert-butyl nitrite, isoamyl nitrite, tert-amylnitrite and an acid, preferably HCl [cf. Organic Syntheses, 31, 96-101; 1951].

Suitable solvents are water, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, and tert.-butanol, moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably water and methanol or ethanol, particularly preferred is water. It is also possible to use mixtures of the solvents mentioned.

Suitable acids and acidic catalysts are in general inorganic acids such as hydrofluoric acid (HF), hydrochloric acid (HCl), hydrobromic acid (HBr), sulphuric acid (H₂SO₄), (HBF₄) tetrafluoro boric acid and perchloric acid (HClO₄). The acids are generally employed in stoichiometric amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

The alkaline or earth alkaline metal nitrite is preferably NaNO₂, KNO₂, or Ca(NO₂)₂. The organic nitrites, is preferably methyl nitrite, ethyl nitrite, n-propyl nitrite, isopropyl nitrite, n-butylnitrite, sec-butyl nitrite, isobutyl nitrite, tert-butyl nitrite, isoamyl nitrite, tert-amylnitrite.

The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of alkaline or earth alkaline metal nitrite or organic nitrites, based on II.

The reduction of IIa to yield I is usually carried out at temperatures of from +20° C. to +100° C., preferably from 50° C. to 95° C., in an inert solvent, in the presence of a reducing agent [cf. Tetrahedron Letters, 41(29), 5567-5569; 2000].

Suitable solvents are alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, and tert.-butanol, moreover DMSO, DMF, and DMA, and water; preferably DMF and water. It is also possible to use mixtures of the solvents mentioned.

Suitable reducing agents are compounds such as hypophosphorous acid or iron (II) sulfate.

The reducing agents are generally employed in stoichiometric amounts; however, they can also be used in excess or, if appropriate, as solvent.

The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of the reducing agent based on IIa.

6-bromo-2,4-dichloro-3-fluoro-aniline of formula II is obtained by bromination of 2,4-dichloro-3-fluoro-aniline of formula III,

Suitable reaction conditions are described in literature (cf. US2010/196321). Suitable bromination agents are bromine, N-bromosuccinimide (“NBS”), dimethyl dibromo hydantoine (DBDMH), dibromoisocyanuric acid (DBI), phenyltrimethylammonium tribromide, copper(II)bromide. The bromination agent is preferably selected from bromine, DBDMH, and NBS. Optionally, an acid can be employed in the reaction such as a Brønsted acid like acetic acid, HBr, HCl, H₂SO₄, oleum with different SO₃-contents, toluene sulphonic acid (TsOH), methane sulfonic acid, or Lewis acids such as AlCl₃·AlBr₃, AlCF₃, Fe-powder, FeCl₃, and FeBr₃. Suitable solvents are halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, or ethers such as tetrahydrofurane (THF), diethylether, tert.-butylmethylether (TBME), 1,4-dioxane, or alcohols such as methanol, ethanol, and the like, or ethyl acetate, butyl acetate, acetic acid, moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), N-methylpyrolidone NMP, dimethylpyrolidinedione DMI and dimethylacetamide (DMA), acetonitrile (AN) or water, or mixtures thereof.

This transformation is usually carried out at temperatures of from 0° C. to +110° C., preferably from 10° C. to +50° C., in an inert solvent, in the presence of hydrogen peroxide [cf. CN 103224452].

Suitable solvents are water, aliphatic hydrocarbons such as pentane, hexane, cyclohexane, and petrol ether, aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, halogenated hydrocarbons such as methylene chloride, chloroform, and chlorobenzene, ethers such as diethylether, diisopropylether, TBME, dioxane, anisole, and THF, nitriles such as acetonitrile, and propionitrile, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, and tert.-butanol, moreover DMSO, DMF, acetic acid and DMA, preferably water and acetic acid. It is also possible to use mixtures of the solvents mentioned.

Suitable acids and acidic catalysts are in general organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, TsOH, benzene sulphonic acid, camphor sulphonic acid, citric acid, and trifluoro acetic acid (TFA). The acids are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

The starting materials are generally reacted with one another in equimolar amounts.

2,4-dichloro-3-fluoro-aniline of formula III is obtained by reduction of 1,3-dichloro-2-fluoro-4-nitro-benzene of formula IV.

This transformation is usually carried out at temperatures of from 0° C. to +120° C., preferably from 10° C. to 70° C., more preferably 10° C. to 40° C., in an inert solvent in the presence of hydrogen and a catalyst [cf. Topics in Catalysis, 55(7-10), 505-511; 2012].

Suitable solvents are water, aliphatic hydrocarbons such as pentane, hexane, cyclohexane, cycloheptane and petrol ether, aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, mesitylene, halogenated hydrocarbons such as methylene chloride, chloroform, and chlorobenzene, dichloro benzenes, benzotrifluoride, ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF, methyltetrahydrofurane, cyclopentyl-methylether, esters such as methyl acetate, ethyl acetate, butyl acetate, ethyl propionate, ethylene carbonate, propylene carbonate, and the like, nitriles such as acetonitrile, and propionitrile, ketones such as acetone, methyl ethyl ketone, diethyl ketone, and tert.-butyl methyl ketone, methyl isopropyl ketone, acetophenone, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, and tert.-butanol, moreover DMSO, sulfolane, DMF, diethyl formamide, NMP, DMI, DMPU and DMA, preferably water, methanol, ethanol, ethyl acetate, or toluene. It is also possible to use mixtures of the solvents mentioned.

Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as LiOH, NaOH, KOH and Ca(OH)₂, alkali metal and alkaline earth metal oxides, such as Li₂O, Na₂O, CaO, and MgO, alkali metal and alkaline earth metal hydrides, such as LiH, NaH, KH, and CaH₂, alkali metal and alkaline earth metal carbonates, such as Li₂CO₃, Na₂CO₃, K₂CO₃ and CaCO₃, and also alkali metal bicarbonates, such as NaHCO₃, moreover, organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidines, lutidines, and 4-dimethylaminopyridine, and also bicyclic amines.

Examples of suitable reducing agents and conditions are known from the literature and can be found inter alia in Advanced Organic Chemistry (ed. J. March), 4^(th) edition, Wiley-Interscience, N Y 1992, p. 1216 ff; or Organikum, 22^(nd) edition, Wiley-VCH, Weinheim 2004, p. 626 ff.

Preferred examples are reducing agents like molecular hydrogen, hydrazine, borane, or borohydrides in combination with a homogeneous or heterogeneous catalysts from metal salts of nickel, palladium, platinum, cobalt, rhodium or iridium and copper. Specific examples include palladium on charcoal, palladium on alumina, platinum on charcoal, platinum(IV) oxide, Raney nickel, rhodium on alumina.

Suitable catalysts are platinum, palladium; nickel and molybdenum.

The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

Suitable acids and acidic catalysts are in general inorganic acids such as HF, HCl, HBr, H₂SO₄ und HClO₄, Lewis acids, such as BF₃, AlCl₃, FeCl₃, SnCl₄, TiCl₄ and ZkCl₂, moreover organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, TsOH, benzene sulphonic acid, camphor sulphonic acid, citric acid, and TFA.

The acids are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of II, based on Ill.

The starting material 1,3-dichloro-2-fluoro-4-nitro-benzene is commercially available or known from the literature [cf. Journal of the American Chemical Society (1959), 81, 94-101] or can be prepared in accordance with the literature cited. 6-bromo-2,4-dichloro-3-fluoro-aniline is known in the art (CAS 1360438-57-8).

The transformation from compound I to active compounds of formula V is known in the art.

The reaction I→VI is usually carried out at temperatures of from −10° C. to 110° C., preferably from 0° C. to 60° C., in an inert solvent, in the presence of a Grignard reagent [cf. WO 2010125130]. The reaction VI→VII is usually carried out at temperatures of from 20° C. to 130° C., preferably from 50° C. to 110° C., in an inert solvent, in the presence of a base [cf. WO 2009126668].

Compounds VII are formed as mixtures of E- and Z-isomers, usually with predominant share of E-isomer. For clarity reasons formula VII is shown as Z-isomer only.

The reaction VII→V is usually carried out at temperatures of from −20° C. to +20° C., preferably from −10° C. to +5° C., in an inert solvent, in the presence of a base and a catalyst [cf. WO 2011067272].

The reaction mixtures are worked up in a customary manner, for example by mixing with water, separating the phases and, if appropriate, chromatographic purification of the crude products. Some of the intermediates and end products are obtained in the form of colourless or slightly brownish viscous oils which are purified or freed from volatile components under reduced pressure and at moderately elevated temperature. If the intermediates and end products are obtained as solids, purification can also be carried out by recrystallization or digestion.

The organic moieties mentioned in the above definitions of the variables are—like the term halogen—collective terms for individual listings of the individual group members. The prefix CO_(n)—C_(m) indicates in each case the possible number of carbon atoms in the group.

The term halogen denotes in each case fluorine, bromine, chlorine, or iodine, in particular fluorine, chlorine, or bromine.

The term “alkyl” as used herein and in the alkyl moieties of alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl and the like refers to saturated straight-chain or branched hydrocarbon radicals having 1 to 2 (“C₁-C₂-alkyl”), 1 to 3 (“C₁-C₃-alkyl”), 1 to 4 (“C₁-C₄-alkyl”), or 1 to 6 (“C₁-C₆-alkyl”). C₁-C₄-Alkyl is methyl (Me), ethyl (Et), propyl, isopropyl, butyl, 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl) or 1,1-dimethylethyl (tert-butyl, ^(t)Bu).

The term “haloalkyl” as used herein, which is also expressed as “alkyl which is partially or fully halogenated”, refers to straight-chain or branched alkyl groups having 1 to 4 (“C₁-C₄-haloalkyl”), carbon atoms (as mentioned above), wherein some or all of the hydrogen atoms in these groups are replaced by halogen atoms as mentioned above: in particular C₁-C₂-haloalkyl.

“Halomethyl” is methyl in which 1, 2 or 3 of the hydrogen atoms are replaced by halogen atoms. Examples are bromomethyl, chloromethyl, fluoromethyl, dichloromethyl, trichloromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl and the like.

The term “alkenyl” as used herein refers to monounsaturated straight-chain or branched hydrocarbon radicals having 2 to 3 (“C₂-C₃-alkenyl”), 2 to 4 (“C₂-C₄-alkenyl”), carbon atoms and a double bond in any position.

The term “alkynyl” as used herein refers to straight-chain or branched hydrocarbon groups having 2 to 3 (“C₂-C₃-alkynyl”), 2 to 4 (“C₂-C₄-alkynyl”) carbon atoms and one or two triple bonds in any position, for example C₂-C₄-alkynyl, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl and the like. The term “cycloalkyl” as used herein refers to mono- or bi- or polycyclic saturated hydrocarbon radicals having 3 to 8 (“C₃-C₈-cycloalkyl”), in particular 3 to 6 (“C₃-C₆-cycloalkyl”) or 3 to 5 (“C₃-C₅-cycloalkyl”) carbon atoms. Examples of monocyclic radicals having 3 to 6 carbon atoms comprise cyclopropyl (c-C₃H₅), cyclobutyl (c-C₄H₇), cyclopentyl (c-C₅H₉) and cyclohexyl (c-C₆H₁₁). Examples of bicyclic radicals having 7 or 8 carbon atoms comprise bicyclo[2.2.1]heptyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl and bicyclo[3.2.1]octyl. Preferably, the term cycloalkyl denotes a monocyclic saturated hydrocarbon radical.

The term “cycloalkyl-C₁-C₄-alkyl” refers to a C₃-C₈-cycloalkyl group (“C₃-C₈-cycloalkyl-C₁-C₄-alkyl”), preferably a C₃-C₆-cycloalkyl group (“C₃-C₆-cycloalkyl-C₁-C₄-alkyl”), more preferably a C₃-C₄-cycloalkyl group (“C₃-C₄-cycloalkyl-C₁-C₄-alkyl”) as defined above (preferably a monocyclic cycloalkyl group) which is bound to the remainder of the molecule via a C₁-C₄-alkyl group, as defined above.

The term “C₁-C₂-alkoxy” is a C₁-C₂-alkyl group, as defined above, attached via an oxygen atom. The term “C₁-C₄-alkoxy” is a C₁-C₄-alkyl group, as defined above, attached via an oxygen atom. The term “C₁-C₆-alkoxy” is a C₁-C₆-alkyl group, as defined above, attached via an oxygen atom. The term “C₁-C₁₀-alkoxy” is a C₁-C₁₀-alkyl group, as defined above, attached via an oxygen atom.

The term “C₁-C₄-alkoxy-methyl” as used herein, refers to methyl in which one hydrogen atom is replaced by a C₁-C₄-alkoxy group, as defined above. The term “C₁-C₆-alkoxy-methyl” as used herein, refers to methyl in which one hydrogen atom is replaced by a C₁-C₆-alkoxy group, as defined above.

The term “SO_(n)—C₁-C₆-alkyl” is a C₁-C₆-alkyl group, as defined above, attached via a sulfur atom, in case n is 0 (also referred to as alkylthio group). If n is 1, the term refers to a C₁-C₆-alkyl group attached via a sulfinyl group (also referred to as alkylsulfinyl group). If n is 2, the term refers to a C₁-C₆-alkyl group attached via a sulfonyl group (also referred to as alkylsulfonyl group).

The substituent “oxo” replaces a CH₂ group by a C(═O) group.

The term “alkylcarbonyl” is a C₁-C₆-alkyl (“C₁-C₆-alkylcarbonyl”), preferably a C₁-C₄-alkyl (“C₁-C₄-alkylcarbonyl”) group, as defined above, attached via a carbonyl [C(═O)] group. Examples are acetyl (methylcarbonyl), propionyl (ethylcarbonyl), propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl and the like. The term “haloalkylcarbonyl” is a C₁-C₆-haloalkyl (“C₁-C₆-haloalkylcarbonyl”), preferably a C₁-C₄-haloalkyl (“C₁-C₄-haloalkylcarbonyl”) group, as defined above, attached via a carbonyl [C(═O)] group.

The term “alkoxycarbonyl” is a C₁-C₆-alkoxy (“C₁-C₆-alkoxycarbonyl”), preferably a C₁-C₄-alkoxy (“C₁-C₄-alkoxycarbonyl”) group, as defined above, attached via a carbonyl [C(═O)] group. The term “C₁-C₄-alkylamino” is a group —N(H)C₁-C₄-alkyl.

The term “C₁-C₄-alkylaminocarbonyl” is a group —C(O)N(H)C₁-C₄-alkyl.

The term “3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-membered saturated, partially or fully unsaturated heterocyclic ring containing 1, 2 or 3 (or 4) heteroatoms N, O, and/or S, as ring members” denotes a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or fully unsaturated heteromonocyclic ring or a 8-, 9- or 10-membered saturated, partially or fully unsaturated heterobicyclic ring containing 1, 2 or 3 (or 4) heteroatoms which are selected from N, O, and S as ring members. Unsaturated rings contain at least one C—C and/or C—N and/or N—N double bond(s). Fully unsaturated rings contain as many conjugated C—C and/or C—N and/or N—N double bonds as allowed by the ring size. Fully unsaturated include aromatic heterocyclic rings. The heterocyclic ring may be attached to the remainder of the molecule via a carbon ring member or via a nitrogen ring member. Of course, the heterocyclic ring contains at least one carbon ring atom. If the ring contains more than one O ring atom, these are not adjacent. N and S ring atoms may be oxidized, if not mentioned otherwise. The oxidized ring atoms constitute an N-oxide, Sulfoxide (SO), and a sulfone (SO₂), resp., wherein the only the N— or S atom is a ring member.

A group of preferred heterocycles is the following: 2-pyridyl (E-1), 3-pyridyl (E-2), 4-pyridyl (E-3), 3-pyridazinyl (E-4), 4-pyrimidinyl (E-5), 2-pyrazinyl (E-6), 2-pyrimidinyl (E-7), thiophen-2-yl (E-8), thiophen-3-yl (E-9), furan-2-yl (E-10), and furan-3-yl (E-11); heterocycles E-1, E-2, and E-7 are particularly preferred, which rings E-1 to E-11 are unsubstituted or substituted by up to 3 same or different substituents.

Another particularly preferred heterocycle is 1,2,4-triazol-1-yl.

Preferred 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully unsaturated heterocyclic rings comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members (HET) are in any positions of formula I, the following: azetidin-3-yl (H-1), dioxin-6-yl (H-2), 1,3-dioxolan-2-yl (H-3), 1,1-dioxotetrahydrothiophene-3-yl (H-4), 1,1-dioxothietan-2-yl (H-5), 1,1-dioxothietan-3-yl (H-6), imidazol-2-yl (H-7), imidazol-4-yl (H-8), imidazol-5-yl (H-9), isothiazol-3-yl (H-10), isothiazol-4-yl (H-11), isothiazol-5-yl (H-12), isoxazol-3-yl (H-13), isoxazol-4-yl (H-14), isoxazol-5-yl (H-15), isoxazolidin-4-yl (H-16), oxazol-2-yl (H-17), oxazol-4-yl (H-18), oxazol-5-yl (H-19), oxethan-3-yl (H-20), 3-oxoisoxazolidin-4-yl (H-21), 2-oxopyrrolidin-3-yl (H-22), 2-oxotetrahydrofuran-3-yl (H-23), [1,3,4]-thiadiazol-2-yl (H-24), [1,2,3]-thiadiazol-4-yl (H-25), [1,2,3]-thiadiazol-5-yl (H-26), thiazol-2-yl (H-27), thiazol-4-yl (H-28), thiazol-5-yl (H-29), thien-2-yl (H-30), thien-3-yl (H-31), thietan-2-yl (H-32), thietan-3-yl (H-33), 1-oxothietan-2-yl (H-34), 1-oxothietan-3-yl (H-35), 1-oxotetrahydrothiophen-3-yl (H-36), tetrahydrofuran-2-yl (H-37), tetrahydrofuran-3-yl (H-38), tetrahydrothiophen-3-yl (H-39), pyrazin-2-yl (E-6), pyrazol-3-yl (H-40), 2-pyridyl (E-1), 3-pyridyl (E-2), 4-pyridyl (E-3), pyridazin-3-yl (E-4), pyridazin-4-yl (H-41), 2-pyrimidinyl (E-7), 4-pyrimidinyl (E-5), 5-pyrimidinyl (H-42), and pyrrolidin-3-yl (H-43). More preferred rings HET are the following: E-1, E-7 and H-6, H-21, H-33 and H-35. Rings E-2 and E-7 are particularly preferred.

In a particular embodiment, the variables of the compounds of the formula V have the following meanings, these meanings, both on their own and in combination with one another, being particular embodiments of the process of the invention.

The process is particularly suitable for compounds V wherein A is selected from A¹, A², and A³.

In the compounds of the inventive process R¹ is preferably fluoromethyl, in particular CF₃.

R³ is preferably H, halogen, or CH₃.

In a preferred embodiment G¹ and G² represent each CR³, particularly G¹ is CH and G² is C—Cl, or C—CH₃.

In another embodiment G¹ and G² represent each CR³, wherein the two R³ form a five- or six membered saturated carbocyclic ring, or a dihydrofurane.

In another embodiment G¹ and G² together form a sulfur atom.

A preferred embodiment relates to the process for obtaining compounds I wherein A is A¹.

The processes for obtaining compounds V wherein A is A¹ start preferably from compounds of formula II wherein A is C(═O)Y, and Y is OR⁹, preferably OH, or C₁-C₄-alkoxy, or NR⁵R⁶, wherein R⁵ and R⁶ are H or C₁-C₄-alkyl, preferably Y is NHCH₃. Particularly preferred A group in compounds I and its intermediates is an C₁-C₄-alkylester, such as C(═O)OCH₃.

In A¹ the variables R⁵ and R⁶ have preferably following meanings:

-   R⁵ is preferably H, C₁-C₄-alkyl; -   R⁶ is preferably H, C₁-C₆-alkyl, C₂-C₆-alkenyl, which groups are     substituted with one or more same or different R⁸, wherein -   R⁸ is preferably C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl, wherein the     carbon chains may be substituted with one or more R¹³;     -   S(O)_(n)R⁹, N(R^(10a))R^(10b), C(═O)N(R^(10a))R^(10b),         C(═S)N(R^(10a))R^(10b), C(═O)OR⁹, CH═NOR⁹, phenyl, which is         unsubstituted or partially or fully substituted with same or         different R¹⁶, or -   a 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully     unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O,     and/or S as ring members, which ring is unsubstituted or partially     or fully substituted with same or different R¹⁶, or

a 5-membered saturated heteromonocyclic ring containing 1, or 2 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or substituted with one or more same or different R¹¹, preferably the unsubstituted or substituted HET;

two R⁸ present on the same carbon atom of an alkyl, alkenyl, alkynyl or cycloalkyl group together form a group ═O, ═C(R¹³)₂; ═S; ═S(O)_(m)(R¹⁵)₂, ═S(O)_(m)R¹⁵N(R^(14a))R^(14b), ═NR^(10a), ═NOR⁹; or ═NN(R^(10a))R^(10b);

-   -   R⁹ is preferably H, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl;

R¹¹ C₁-C₁₀-alkyl, which is unsubstituted, partially or fully halogenated, and/or may be substituted with same or different R⁸, or

-   -   OR⁹, NR^(10a)R^(10b), S(O)_(n)R⁹;     -   two R¹¹ present on the same ring carbon atom of an unsaturated         or partially unsaturated heterocyclic ring may together form a         group ═O, ═C(R¹³)₂, ═S, ═S(O)_(m)(R¹⁵)₂,         ═S(O)_(m)R¹⁵N(R^(14a))R^(14b), ═NR¹⁴, ═NOR¹⁵, or         ═NN(R^(14a))R^(14b).

Another embodiment relates to the process for obtaining compounds V wherein A is A², preferably wherein Q-Z is %—CH₂—O—*, and R⁴ is C₁-C₄-alkylcarbonyl wherein the terminal C-atom of the alkyl is substituted with S(O)_(n)—C₁-C₄-alkyl.

Another embodiment relates to the process for obtaining compounds V wherein A is A³, preferably CH₂—NR⁵C(═O)R⁶, wherein R⁵ is H or CH₃, and R⁶ is H, C₁-C₆-alkyl, C₂-C₆-alkenyl, which groups are substituted with one or more same or different R⁸, wherein R⁸ is as defined and preferred above.

Compounds V and its sub formulae wherein A is A⁴ are intermediates in the inventive process.

The process is particularly suitable for synthesis of following active compounds of formula V, which correspond to formulae V.A, and V.B, wherein the variables are as defined and preferred above:

wherein W is CH or O; and

wherein p is 1 or 2; R^(x5) is H or CH₃, and R^(x6) is C₁-C₆-alkyl, C₁-C₄-haloalkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl, which groups may be substituted with C(═O)OR^(a1), C(═O)N(R^(a2))R^(a3), CH═NOR^(a1), and phenyl, benzyl, which rings are unsubstituted or substituted with halogen, C₁-C₄-alkyl, or C₁-C₄-haloalkyl; wherein R^(a1) is C₁-C₆-alkyl, R^(a2) and R^(a3) are each H or C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₄-alkenyl, C₂-C₄-alkynyl.

Preferably R^(x6) is CH₃, C₂H₅, CH₂(CH₃)₂, CH₂CH═CH₂, CH₂CF₃, CH₂CH₂CF₃, CH₂C₆H₅, or CH₂C(═O)OCH₃.

Preferably G¹, and G² are each CR³; wherein each R³ is H, halogen, or C₁-C₆-alkyl, particularly G¹, is CH, and G² is CR³; wherein R³ is halogen, or C₁-C₂-alkyl.

The process is furthermore particularly suitable for synthesis of following active compounds V.1, and V.2 of formula V which are known in the art (cf.: WO 2011/067272; WO 2012/120399):

Accordingly, the process is furthermore particularly suitable for synthesis of compounds of formula V, wherein

-   R¹ is CF₃; -   R^(2a) is F, Cl, Br, CF₃, or OCF₃; -   R^(2b) and R^(2c) are independently from each other H, F, Cl, Br,     CF₃, or OCF₃; -   A is A¹, A², or A³; wherein     -   A¹ is C(═O)N(R⁵)R⁶, C(═O)OR⁹, wherein     -   A² is

-   -   wherein #denotes the bond of group A, and % denotes the bond to         G¹;     -   Q-Z is %—CH₂—O—*, wherein % marks the bond of Q to phenyl, and         *the bond of Z to azetidin; and     -   R^(A4) is H, or C(═O)R^(4A), wherein     -   R^(4A) is H, C₁-C₄-alkylcarbonyl, which is unsubstituted or         substituted with S(O)_(n)—C₁-C₆-alkyl;     -   A³ is CH₂—NR⁵C(═O)R⁶;

-   G¹, and G² are each CR³, or together form a sulfur atom;     -   R³ is H or C₁-C₄-alkyl, or two R³ bonded to adjacent carbon         atoms may form a five- or six membered saturated or aromatic         carbocyclic ring, or a dihydrofurane, or     -   R³ bonded to a carbon atom in position G¹ form a bond to the         chain *-Q-Z— in group A²;     -   R⁵ is H;     -   R⁶ is H, or C₁-C₆-alkyl which is unsubstituted, or substituted         with one or two R⁸;     -   or R⁵ and R⁶, together with the nitrogen atom to which they are         bound, form a 5- or 6-membered saturated, heterocyclic ring,         which ring contain 1 or 2 groups selected from O, S, N, and C═O         as ring members, which heterocyclic ring is unsubstituted or         partially substituted with same or different C₁-C₆-alkyl,         C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy,         C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, C₃-C₈-cycloalkyl,         C₃-C₈-halocycloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl,         C₂-C₆-alkynyl, C₂-C₆-haloalkynyl;     -   each R⁸ is C(═O)N(R^(10a))R^(10b), or     -   two R⁸ present on the same carbon atom of an alkyl group         together form ═NOR⁹;     -   R⁹ being C₁-C₄-alkyl;     -   R^(10a), R^(10b) are independently from one another H,         C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl,         C₂-C₆-alkynyl, C₂-C₆-haloalkynyl.

Such compounds represent formula Va.

The following examples illustrate the invention.

EXAMPLES A. Preparation Examples

With appropriate modification of the starting materials, the procedures given in the synthesis description were used to obtain further compounds I. The compounds obtained in this manner are listed in the table that follows, together with physical data.

The products shown below were characterized by melting point determination, by NMR spectroscopy or by the masses ([m/z]) or retention time (RT; [min.]) determined by HPLC-MS or HPLC spectrometry.

HPLC-MS=high performance liquid chromatography-coupled mass spectrometry;

HPLC method A: HPLC Phenomenex Kinetex 1.7 μm XB-C18 100 A, 50×2.1 mm″, Mobile Phase: A: water+0.1% TFA; B:CAN; Temperature: 60° C.; Gradient:5% B to 100% B in 1.50 min; 100% B 0.25 min; Flow: 0.8 ml/min to 1.0 ml/min in 1.51 min; MS method: ESI positive; Mass range (m/z): 100-700″.

HPLC method B: HPLC method: Phenomenex Kinetex 1.7 μm XB-C18 100 A; 50×2.1 mm; mobile phase: A: water+0.1% trifluoroacetic acid (TFA); B: acetonitrile; gradient: 5-100% B in 1.50 minutes; 100% B 0.25 min; flow: 0.8-1.0 ml/min in 1.51 minutes at 60° C. MS: ESI positive, m/z 100-1400.

Example 1: Preparation of 2,4-dichloro-3-fluoro-aniline

A mixture of 1,3-dichloro-2-fluoro-4-nitro-benzene (24.9 g, 0.119 mol, 1.00 equiv.), Pt/C 5%/V 2.5% (2.00 g) and methanol (250 mL) was charged into a hydrogenation apparatus and flushed with hydrogen gas. A constant pressure of 0.1 bar hydrogen was kept throughout the reaction and the mixture was stirred at 2000 rpm keeping the temperature between 24-27° C. by cooling. After 0.5 h, the reaction was completed, and the catalyst was filtered off using a plug of celite. The filtrate was concentrated in vacuum to yield the title compound (21.1 g, purity 93%, yield 92%).

¹H NMR: (400 MHz, CDCl₃): δ 4.09 (br. s, 2H), 6.60 (m, 1H), 7.06 (m, 1H) ppm.

Example 2: Preparation of 6-bromo-2,4-dichloro-3-fluoro-aniline

To a mixture of 2,4-dichloro-3-fluoro-aniline (20.9 g, 0.110 mmol, 1.00 equiv.) and glacial acetic acid (92.7 g, 1.54 mol, 14 equiv.) was added bromine (10.58 g, 0.066 mol, 0.600 equiv.) at 20-22° C. within 25 min. After 5 min, hydrogen peroxide solution (50% in water, 4.502 g, 0.066 mol, 0.600 equiv.) was added and the temperature was maintained between 20-22° C. After 15 min, the reaction was completed and poured onto ice-water (300 mL). Excess of bromine was quenched by the addition of aqueous sodium sulfite solution. The resulting solids were collected by filtration and washed with water. Drying in vacuum at 40° C. yielded the title compound (29.60 g, purity 95%, yield 99%)

¹H NMR: (400 MHz, CDCl₃): δ 4.61 (br. s, 2H), 7.40 (m, 1H) ppm.

Example 3: Preparation of 5-bromo-1,3-dichloro-2-fluoro-benzene

A mixture of 6-bromo-2,4-dichloro-3-fluoro-aniline (29.5 g, 0.108 mmol, 1.00 equiv.) and concentrated hydrochloric acid (32% in water, 117 mL. 1.19 mol, 11 equiv.) was kept at 50° C. for 10 min and water was added. The resulting suspension was cooled to 0° C. and an aqueous solution of sodium nitrite (40.62 g, 25%, 0.147 mol, 1.40 equiv.) was added within 30 min, keeping the temperature between 0-2° C. for 1 h.

In a second flask, an aqueous solution of hypophosphoric acid (528 g, 50%, 4.01 mol, 37 equiv.) was heated to 90° C. and the diazonium solution from above was added within 10 min. After another 20 min at 85-90° C., the reaction was complete. The mixture was cooled and extracted with methylene chloride, combined organic layers were washed with water and dried over anhydrous magnesium sulfate. After filtration, the mother liquid was concentrated in vacuum to yield the title compound (23.5 g, purity 93%, yield 83%).

¹H NMR: (400 MHz, CDCl₃): δ 7.46 (m, 1H) ppm. 

The invention claimed is:
 1. A process for preparing 5-bromo-1,3-dichloro-2-fluoro-benzene comprising diazotizing 6-bromo-2,4-dichloro-3-fluoro-aniline and reducing the resulting diazonium salt to yield 5-bromo-1,3-dichloro-2-fluoro-benzene.
 2. The process of claim 1, wherein 6-bromo-2,4-dichloro-3-fluoro-aniline is obtained by brominating 2,4-dichloro-3-fluoro-aniline.
 3. The process of claim 2, wherein 2,4-dichloro-3-fluoro-aniline is obtained by reducing 1,3-dichloro-2-fluoro-4-nitro-benzene.
 4. The process of claim 3, wherein the reduction is conducted with hydrogen on Pd/C catalyst.
 5. The process of claim 2, wherein the bromination is conducted with bromine and an oxidation agent.
 6. The process of claim 5, wherein the oxidation agent is H₂O₂.
 7. The process of claim 1, wherein the diazotization is conducted with NaNO₂.
 8. The process of claim 1, wherein the reduction of the diazonium salt is effected with hypophosphoric acid.
 9. 6-bromo-2,4-dichloro-3-fluoro-aniline.
 10. A process for preparing a compound of formula V

wherein X is CH, O, or S, U is CH or N; each R² is independently H, halogen, CN, N₃, NO₂, SCN, SF₅, C₁-C₆-alkyl, C₃-C₈-cycloalkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted with one or more same or different R⁸, Si(R¹²)₃, OR⁹, S(O)_(n)R⁹, NR^(10a)R^(10b), phenyl which is unsubstituted or partially or fully substituted with R¹¹, and a 3- to 10-membered saturated, partially or fully unsaturated heteromonocyclic or heterobicyclic ring containing 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or substituted with one or more same or different R¹¹; n is 0, 1, or 2; G¹, G² are each CR³, or together form a sulfur atom; each R³ is independently selected from the meanings mentioned for R², or two R³ bonded to adjacent carbon atoms may form a five- or six membered saturated, partially or fully unsaturated carbocyclic ring, or a dihydrofurane, or R³ bonded to carbon atom in position G¹ form a bond to the chain *-Q-Z— in group A²; A is a group A¹, A², A³, or A⁴; wherein A¹ is C(═W)Y; W is O, or S; Y is N(R⁵)R⁶, or OR⁹; A² is

wherein #denotes the bond of group A, and % denotes the bond to G¹; Q-Z is %—CH₂—O—*, %—CH₂—S(O)_(n)—*, or %—C(═O)—O—*, wherein % marks the bond of Q to phenyl, and *the bond of Z to azetidin; and R^(A4) is H or C(═O)R^(4A), wherein R^(4A) is H, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, C₂-C₆-haloalkynyl, C₁-C₄-alkylcarbonyl, which aliphatic groups are unsubstituted or substituted with one or more radicals R⁴¹; C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl which cyclic groups are unsubstituted or substituted with one or more R⁴²; C(═O)N(R⁴³)R⁴⁴, N(R⁴³)R⁴⁵, CH═NOR⁴⁶; phenyl, heterocycle, or hetaryl HET which rings are unsubstituted or partially or fully substituted with R^(A); R⁴¹ is independently OH, CN, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, S(O)_(n)C₁-C₆-alkyl, S(O)_(n)C₁-C₆-haloalkyl, C(═O)N(R⁴³)R⁴⁴, C₃-C₆-cycloalkyl, or C₃-C₆-halocycloalkyl which cycles are unsubstituted or substituted with one or more R⁴¹¹; or phenyl, heterocycle or hetaryl HET which rings are unsubstituted or partially or fully substituted with R^(A); R⁴¹¹ is independently OH, CN, C₁-C₂-alkyl, or C₁-C₂-haloalkyl; R⁴³ is H, or C₁-C₆-alkyl, R⁴⁴ is H, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, C₂-C₆-haloalkynyl, or C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, C₃-C₆-cycloalkylmethyl, or C₃-C₆-halocycloalkylmethyl which rings are unsubstituted or substituted with a cyano; R⁴⁵ H, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₄-alkenyl, C₂-C₄-alkynyl, CH₂—CN, C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, C₃-C₆-cycloalkylmethyl, C₃-C₆-halocycloalkylmethyl, phenyl and hetaryl HET which aromatic rings are unsubstituted or partially or fully substituted with R^(A); R⁴² C₁-C₆-alkyl, C₁-C₆-haloalkyl, or a group as defined for R⁴¹; R⁴⁶ is independently H, C₁-C₆-alkyl, or C₁-C₆-haloalkyl; R^(A) is independently selected from halogen, CN, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl, C₂-C₄-alkynyl, C₂-C₄-haloalkynyl, C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, S(O)_(n)—C₁-C₄-alkyl, S(O)_(n)—C₁-C₄-haloalkyl, C₁-C₄-alkylcarbonyl, C₁-C₄-haloalkylcarbonyl, C(═O)N(R⁴³)R⁴⁴; or two R^(A) present on the same carbon atom of a saturated or partially saturated ring may form together ═O or ═S; or two R^(A) present on the same S or SO ring member of a heterocyclic ring may together form a group ═N(C₁-C₆-alkyl), ═NO(C₁-C₆-alkyl), ═NN(H)(C₁-C₆-alkyl) or ═NN(C₁-C₆-alkyl)₂; A³ is CH₂—NR⁵C(═W)R⁶; A⁴ is cyano; R⁵ is independently selected from the meanings mentioned for R²; R⁶ is H, CN, C₁-C₁₀-alkyl, C₃-C₈-cycloalkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted with one or more same or different R⁸; or S(O)_(n)R⁹, or C(═O)R⁸; a 3- to 8-membered saturated, partially or fully unsaturated heterocyclic ring, which ring may contain 1, 2, 3, or 4 heteroatoms O, S, N, C═O and/or C═S as ring members, which heterocyclic ring is unsubstituted or partially or fully substituted with same or different halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, C₂-C₆-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R⁸, or phenyl which may be partially or fully substituted with R¹¹; or R⁵ and R⁶, together with the nitrogen atom to which they are bound, form a 3-to 8-membered saturated, partially or fully unsaturated heterocyclic ring, which ring may contain 1, 2, 3, or 4 heteroatoms O, S, N, C═O and/or C═S as ring members, which heterocyclic ring is unsubstituted or partially or fully substituted with same or different halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, C₂-C₆-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R⁸, or phenyl which may be partially or fully substituted with R¹¹; or R⁵ and R⁶ together form a group ═C(R⁸)₂, ═S(O)_(m)(R⁹)₂, ═NR^(10a), or ═NOR⁹; R^(7a), R^(7b) are each independently H, halogen, CN, C₁-C₆-alkyl, C₃-C₈-cycloalkyl, C₂-C₆-alkenyl, or C₂-C₆-alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted with same or different R⁸; each R⁸ is independently CN, N₃, NO₂, SCN, SF₅, C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl, wherein the carbon chains may be substituted with one or more R¹³; Si(R¹²)₃, OR⁹, OSO₂R⁹, S(O)_(n)R⁹, N(R^(10a))R^(10b), C(═O)N(R^(10a))R^(10b), C(═S)N(R^(10a))R^(10b), C(═)OR⁹, CH═NOR⁹, phenyl, which is unsubstituted or partially or fully substituted with same or different R¹⁶, or a 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted or partially or fully substituted with same or different R¹⁶, or two R⁸ present on the same carbon atom of an alkyl, alkenyl, alkynyl or cycloalkyl group together form a group ═O, ═C(R¹³)₂; ═S; ═S(O)_(m)(R¹⁵)₂, ═S(O)_(m)R¹⁵N(R^(14a))R^(14b), ═NR^(10a), ═NOR⁹; or ═NN(R^(10a))R^(10b); or two radicals R⁸, together with the carbon atoms of the alkyl, alkenyl, alkynyl or cycloalkyl group which they are bonded to, form a 3-, 4-, 5-, 6-, 7- or 8-membered saturated or partially unsaturated carbocyclic or heterocyclic ring, which heterocyclic ring comprises 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, and which ring is unsubstituted, or partially or fully substituted with same or different R¹⁶; and R⁸ as a substituent on a cycloalkyl ring may additionally be C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, and C₂-C₆-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R¹³; and R⁸ in the groups C(═O)R⁸ and ═C(R⁸)₂ may additionally be H, halogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, or C₂-C₆-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R¹³; each R⁹ is independently H, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₃-C₈-cycloalkyl, C₃-C₈-cycloalkyl-C₁-C₄-alkyl-, C₃-C₈-halocycloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, or C₂-C₆-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R¹³, or C₁-C₆-alkyl-C(═O)OR¹⁵, C₁-C₆-alkyl-C(═O)N(R^(14a))R^(14b), C₁-C₆-alkyl-C(═S)N(R^(14a))R^(14b), C₁-C₆-alkyl-C(═NR¹⁴)N(R^(14a))R^(14b), Si(R¹²)₃, S(O)_(n)R¹⁵, S(O)_(n)N(R^(14a))R^(14b), N(R^(10a))R^(10b), N═C(R¹³)₂, C(═O)R¹³, C(═O)N(R^(14a))R^(14b), C(═S)N(R^(14a))R^(14b), C(═O)OR¹⁵, or phenyl, which is unsubstituted, or partially or fully substituted with R¹⁶; and a 3- to 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R¹⁶; and R⁹ in the groups S(O)_(n)R⁹ and OSO₂R⁹ may additionally be C₁-C₆-alkoxy, or C₁-C₆-haloalkoxy; R^(10a), R^(10b) are independently from one another H, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, C₂-C₆-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R¹³; C₁-C₆-alkyl-C(═O)OR¹⁵, C₁-C₆-alkyl-C(═O)N(R^(14a))R^(14b), C₁-C₆-alkyl-C(═S)N(R^(14a))R^(14b), C₁-C₆-alkyl-C(═NR¹⁴)N(R^(14a))R^(14b), C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, S(O)_(n)R¹⁵, S(O)_(n)N(R^(14a))R^(14b), C(═O)R¹³, C(═O)OR¹⁵, C(═O)N(R^(14a))R^(14b), C(═S)R¹³, C(═S)SR¹⁵, C(═S)N(R^(14a))R^(14b), C(═NR¹⁴)R¹³; phenyl, which is unsubstituted, or partially or fully substituted with same or different R¹⁶; and a 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R¹⁶; or R^(10a) and R^(10b) together with the nitrogen atom they are bonded to form a 3- to 8-membered saturated, partially or fully unsaturated heterocyclic ring, which ring may additionally contain one or two heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different halogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, C₂-C₆-haloalkynyl, phenyl which may be partially or fully substituted with R¹⁶, and a 3-, 4-, 5-, 6-, or 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R¹⁶; or R^(10a) and R^(10b) together form a group ═C(R¹³)₂, ═S(O)_(m)(R¹⁵)₂, ═S(O)_(m)R¹⁵N(R^(14a))R^(14b), ═NR¹⁴, or ═NOR¹⁵; R¹¹ is halogen, CN, N₃, NO₂, SCN, SF₅, C₁-C₁₀-alkyl, C₃-C₈-cycloalkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, which groups are unsubstituted, partially or fully halogenated, and/or may be substituted with same or different R⁸, or OR⁹, NR^(10a)R^(10b), S(O)_(n)R⁹, Si(R¹²)₃; phenyl, which is unsubstituted, or partially or fully substituted with same or different R¹⁶; and a 3- to 7-membered saturated, partially or fully unsaturated aromatic heterocyclic ring comprising 1, 2, 3, or 4 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R¹⁶; or two R¹¹ present on the same ring carbon atom of an unsaturated or partially unsaturated heterocyclic ring may together form a group ═O, ═C(R¹³)₂, ═S, ═S(O)_(m)(R¹⁵)₂, ═S(O)_(m)R¹⁵N(R^(14a))R¹⁴b, ═NR¹⁴, ═NOR¹⁵, or ═NN(R^(14a))R^(14b); or two R¹¹ bound on adjacent ring atoms form together with the ring atoms to which they are bound a saturated 3- to 9-membered ring, which ring may contain 1 or 2 heteroatoms O, S, N, and/or NR¹⁴, and/or 1 or 2 groups C═O, C═S, C═NR¹⁴ as ring members, and which ring is unsubstituted, or partially or fully substituted with same or different halogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl, C₂-C₆-haloalkynyl, phenyl which may be partially or fully substituted with same or different R¹⁶, and a 3- to 7-membered saturated, partially or fully unsaturated heterocyclic ring containing 1, 2, or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R¹⁶; each R¹² is independently C₁-C₄-alkyl and phenyl, which is unsubstituted, or partially or fully substituted with same or different C₁-C₄-alkyl; each R¹³ is independently CN, NO₂, OH, SH, SCN, SF₅, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, SO_(n)—C₁-C₆-alkyl, SO_(n)—C₁-C₆-haloalkyl, Si(R¹²)₃, —C(═O)N(R^(14a))R^(14b), C₃-C₈-cycloalkyl which is unsubstituted, partially or fully halogenated or substituted with 1 or 2 same or different C₁-C₄-alkyl, C₃-C₄-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy and/or oxo; phenyl, benzyl, phenoxy, where the phenyl moiety may be substituted with one or more same or different R¹⁶; and a 3- to 7-membered saturated, partially or fully unsaturated heterocyclic ring containing 1, 2, or 3 heteroatoms N, O, and/or S, as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R¹⁶; or two R¹³ present on the same carbon atom of an alkyl, alkenyl, alkynyl or cycloalkyl group may together be ═O, ═CH(C₁-C₄-alkyl), ═C(C₁-C₄-alkyl)C₁-C₄-alkyl, ═N(C₁-C₆-alkyl) or ═NO(C₁-C₆-alkyl); and R¹³ as a substituent of a cycloalkyl ring may additionally be C₁-C₆-alkyl, C₂-C₆-alkenyl or C₂-C₆-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted with 1 or 2 CN, C₃-C₄-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, and oxo; and R¹³ in groups ═C(R¹³)₂, N═C(R¹³)₂, C(═O)R¹³, C(═S)R¹³, and C(═NR¹⁴)R¹³ may additionally be H, halogen, C₁-C₆-alkyl, C₂-C₆-alkenyl, or C₂-C₆-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted with 1 or 2 CN, C₃-C₄-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, and oxo; each R¹⁴ is independently H, CN, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, SO_(n)—C₁-C₆-alkyl, SO_(n)—C₁-C₆-haloalkyl, Si(R¹²)₃; C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted with 1 or 2 CN, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, SO_(n)—C₁-C₄-alkyl, C₃-C₆-cycloalkyl which is unsubstituted or substituted with 1 or 2 substituents halogen and CN; and oxo; C₃-C₈-cycloalkyl which is unsubstituted, or partially or fully halogenated or substituted with 1 or 2 CN, C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, SO_(n)—C₁-C₆-alkyl, C₃-C₄-cycloalkyl, C₃-C₄-cycloalkyl-C₁-C₄-alkyl-, which groups are unsubstituted, or substituted with 1 or 2 substituents selected from halogen and CN; phenyl, benzyl, pyridyl, phenoxy, which cyclic moieties are unsubstituted, or substituted with one or more same or different halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl, C₂-C₄-alkynyl, C₂-C₄-haloalkynyl, C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, and C₁-C₆-alkoxycarbonyl; and a 3-, 4-, 5- or 6-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R¹⁶; R^(14a) and R^(14b) independently of each other, have one of the meanings given for R¹⁴; or R^(14a) and R^(14b), together with the nitrogen atom to which they are bound, form a 3-to 7-membered saturated, partially, or fully unsaturated heterocyclic ring, wherein the ring may additionally contain 1 or 2 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, or C₁-C₄-haloalkoxy; or R^(14a) and R¹⁴ or R^(14b) and R¹⁴, together with the nitrogen atoms to which they are bound in the group C(═NR¹⁴)N(R^(14a))R^(14b), form a 3- to 7-membered partially, or fully unsaturated heterocyclic ring, wherein the ring may additionally contain 1 or 2 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different halogen, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, or C₁-C₄-haloalkoxy; each R¹⁵ is independently H, CN, Si(R¹²)3 C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted with 1 or 2 radicals C₃-C₄-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, SO_(n)—C₁-C₆-alkyl, or oxo; C₃-C₈-cycloalkyl which is unsubstituted, partially or fully halogenated or substituted with 1 or 2 radicals C₁-C₄-alkyl, C₃-C₄-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, SO_(n)—C₁-C₆-alkyl, or oxo; phenyl, benzyl, pyridyl, and phenoxy, which rings are unsubstituted, partially or fully halogenated, or substituted with 1, 2 or 3 substituents C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, or (C₁-C₆-alkoxy)carbonyl; each R¹⁶ is independently halogen, NO₂, CN, OH, SH, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, SO_(n)—C₁-C₆-alkyl, SO_(n)—C₁-C₆-haloalkyl, C₁-C₄-alkylcarbonyl, C₁-C₄-haloalkylcarbonyl, C₁-C₄-alkoxycarbonyl, C₁-C₄-haloalkoxycarbonyl, aminocarbonyl, C₁-C₄-alkylaminocarbonyl, di-(C₁-C₄-alkyl)-aminocarbonyl, Si(R¹²)₃; C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted with 1 or 2 radicals CN, C₃-C₄-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, or oxo; C₃-C₈-cycloalkyl which is unsubstituted, partially or fully halogenated or substituted with 1 or 2 radicals CN, C₁-C₄-alkyl, C₃-C₄-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, or oxo; phenyl, benzyl, pyridyl and phenoxy, which rings are unsubstituted, partially or fully halogenated, or substituted with 1, 2 or 3 substituents C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, or (C₁-C₆-alkoxy)carbonyl; or two R¹⁶ present together on the same atom of an unsaturated or partially unsaturated ring may be ═O, ═S, ═N(C₁-C₆-alkyl), ═NO—C₁-C₆-alkyl, ═CH(C₁-C₄-alkyl), or ═C(C₁-C₄-alkyl)₂; or two R¹⁶ on two adjacent carbon atoms form together with the carbon atoms they are bonded to a 4- to 8-membered saturated, partially or fully unsaturated ring, wherein the ring may contain 1 or 2 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, or C₁-C₄-haloalkoxy; each m is independently 0, or 1; comprising preparing 5-bromo-1,3-dichloro-2-fluoro-benzene according to claim 1, further transforming it to VI,

reacting VI to VII,

and cyclizing VII to yield V.
 11. The process of claim 10, wherein the formula V corresponds to formula V.A

wherein W is CH or O, R⁵ is H or CH₃, and R⁶ is H, C₁-C₆-alkyl, or C₂-C₆-alkenyl.
 12. The process of claim 10, wherein the formula V corresponds to formula V.B

wherein G¹ is CH, and G² is CR³; wherein R³ is halogen, or C₁-C₂-alkyl; p is 1 or 2; R^(x5) is H or CH₃, and R^(x6) is CH₃, C₂H₅, CH₂(CH₃)₂, CH₂CH═CH₂, CH₂CF₃, CH₂CH₂CF₃, CH₂C₆H₅, or CH₂C(═O)OCH₃. 